安进（Amgen）4月5日公布了实验性溶瘤免疫疗法talimogene laherparepvec（T-Vec）黑色素瘤关键性III期研究的总生存期（OS）初步分析数据。该项研究在可注射未切除IIIB、IIIC、IV期黑色素瘤（melanoma）患者中开展，将T-Vec疗法与皮下注射粒细胞-巨噬细胞集落刺激因子（GM-CSF）疗法进行了对比。数据表明，该项研究达到了持久反应率（DRR）的主要终点（如此前所报道），但未达到改善总生存期（OS）的次要终点，尽管T-Vec治疗组表现出强烈的有利趋势（p=0.051）。
此前，2013年6月公布的积极数据表明，该项研究达到了持久反应率（DRR）的主要终点，其定义为完全或部分反应缓解持续至少6个月。T-Vec组总缓解率为26%，GM-CFS组为6%。既定中期分析也观察到了总生存期（HR=0.79，95％CI，0.61-1.02）的积极趋势。
今年3月，安进公布了该项研究的回顾性分析数据，记录到了肿瘤层面的反应率（tumor-level response）。数据显示，T-Vec缩小了已注射该药的肿瘤的体积，同时也缩小了转移至身体其他部位的肿瘤的体积，表明T-Vec触发了系统性（全身性）免疫反应。
ISI集团分析师Mark Schoenebaum指出，T-Vec未能显著改善黑色素瘤患者整体存活率，可能会影响该药的获批并限制其商业前景。
关于
Talimogene laherparepvec(T-Vec)是一种实验性溶瘤免疫疗法（oncolytic immunotherapy），是一种基因工程化的病毒，能够表达GM-CFS。T-Vec直接注射入肿瘤，并能够在肿瘤细胞中复制直至细胞膜破裂及死亡（即细胞裂解），同时能够在肿瘤组织局部释放GM-CSF，这是一种白细胞生长因子，能够激活全身性免疫反应。T-Vec通过2种重要且互补的方式发挥作用：引发肿瘤组织溶解，同时激发一种全身性的抗肿瘤免疫反应。
该领域中，其他的新药包括免疫疗法（immunotherapies），如百时美施贵宝（BMS）的Yervoy，该疗法旨在利用人体的免疫系统来对抗黑色素瘤。目前，Amgen也正在其他类型肿瘤中评价T-Vec。同时也正在评价T-Vec和Yervoy组合疗法，并已同意开展研究调查T-Vec与默沙东PD-抑制剂组合疗法。
Amgen melanoma drug fails to improve overall survival rates
THOUSAND OAKS, Calif., April 4, 2014 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced top-line results from the primary overall survival (OS) analysis of a Phase 3 trial in melanoma, which eva1uated the efficacy and safety of talimogene laherparepvec for the treatment of unresected stage IIIB, IIIC or IV melanoma compared to treatment with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Results showed that, while the primary end point of durable response rate was met (as previously reported), the secondary endpoint of OS was not met, although there was a strong trend in favor of talimogene laherparepvec (p=0.051). The estimated OS hazard ratio and improvement in median OS were similar to what was previously reported at the interim OS analysis.
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors and to initiate an immune response to target cancer that has me-tastasized, or spread to other areas of the body.
"We remain encouraged that the study met its primary endpoint of achieving durable responses in patients with me-tastatic melanoma," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We missed statistical significance on the secondary endpoint of overall survival but the strong trend in survival benefit supports further research of talimogene laherparepvec to better understand its role in melanoma, both as a single-agent and in combination with other therapies."
The global, randomized, open-label Phase 3 trial enrolled patients with unresected stage IIIB, IIIC or IV melanoma. Patients were randomized 2:1 to receive either talimogene laherparepvec every two weeks through direct tumor injection or GM-CSF subcutaneously for the first 14 days of each 28-day cycle, for up to 18 months.
The most frequent adverse events observed in this trial were fatigue, chills and pyrexia. The most common serious adverse events include disease progression, cellulitis and pyrexia.
ab0ut Talimogene Laherparepvec
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have me-tastasized. Talimogene laherparepvec was designed to work in two imp0rtant and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor's cells causing the cell to rupture and die in a process called lysis. The rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, that can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body.
ab0ut Melanoma
Melanoma is a type of skin cancer that is characterized by the uncontrolled growth of melanocytes, which are the cells responsible for providing the pigment to skin.1 Melanoma is the most aggressive and serious form of skin cancer. Currently, 132,000 melanoma cases occur globally each year.2 In the U.S., while melanoma accounts for less than five percent of skin cancer cases, it causes the most skin cancer deaths.2 The number of new cases of melanoma in the U.S. has been increasing for the last 30 years.2
Melanoma is considered to be advanced when it has spread, or me-tastasized, from the origin site to deeper parts of the skin or other organs such as the lymph nodes, lungs or other parts of the body distant from the primary tumor site.
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